Using cyproterone acetate (CA) is a safe and well-tolerated approach for treating gender dysphoria in adolescent trans-girls, according to new research published in the Journal of Sexual Medicine. The approach may also offer an alternative to using gonadotropin-releasing analogues (GnRHas), the researchers added.

Gender dysphoria refers to a mismatch between one’s birth gender and preferred gender. Often, individuals with gender dysphoria feel as though they have been born in the wrong gender and wish to transition to the gender with which they are more comfortable.

Some people develop gender dysphoria as children. As they start puberty, they may start medical therapy to suppress hormones responsible for the development of secondary sex characteristics. This allows them more time to decide on their transition path. It might also minimize the amount of sex reassignment surgery needed later.

Many patients use GnRHas for this first step. But this approach can be expensive, and it is unclear how effective it is during later stages of puberty.

Research suggests that combining estrogens with CA therapy can further decrease the effects of androgens in trans-girls. Thus, the current study investigated the safety of CA on its own and in combination with estrogens for trans-girls seeking a male-to-female transition in late puberty.

Twenty-seven trans-girls in Belgium participated in the study. All of them underwent CA therapy for an average of 12 months. A subgroup of 21 trans-girls (who were at least 16 years old) went on to add estrogens to their CA treatment for an average of sixteen months. (The remaining six girls were too young to start with estrogens.) Estrogen doses were gradually increased over time. All the trans-girls received counseling throughout the study period.

During CA treatment alone, more than half of the participants said they needed to shave facial hair less often. About a third began developing breasts, although this result became more common when estrogens were added to the regimen. Participants also reported fatigue during the CA phase; this resolved for most with the addition of estrogens. During the CA plus estrogens phase, breast tenderness, increased hunger, and emotionality were common. No adverse events were reported.

Total and free testosterone levels declined over the treatment period, eventually falling below the typical amounts for adolescent males. However, testosterone levels did not drop to levels generally found in females.

The authors noted that breast development was “poor,” even with the addition of estrogens. Since estrogens were well-tolerated, they suggested starting this phase at higher doses or with faster dose increments.

“Although direct comparative studies need to be performed first, we suggest that, if confirmed, CA could offer a safe and valuable alternative for GnRHa,” they concluded.